Abstract B16: Indigeneously synthesized inorganic coordination complex act as apoptotic agent in cancerous cells

Abstract

Abstract Objective: Metal complexes play an important role in chemotherapy. Arguably the most prominent metal complex in medicine is the anticancer agent cisplatin (cis-diamineplatinum (II) dichloride). Cisplatin and other chemotherapeutic metal complexes also have certain reported side effects and their cost is very high for a country like India. In the present study we aim to evaluate the effect of novel inorganic coordination complexes in comparison to cisplatin in the treatment of cancer of different origin such as lung, cervix, and ovary. Method: The decrease in cell viability was determined by MTT assay followed by wound healing and DNA hypoploidy assay Apoptosis has been studied by Annexin V-FITC/PI dual staining flow cytometric assay. Following this: (1) chromosomal condensation by DAPI staining, (2) determination of ROS generation by DCFDA staining, and (3) measurement of altered mitochondrial membrane potential with JC1 dyes was performed. Changes in Bcl 2/Bax ratio and release of Cytochrome-C protein by Western blot technique confirm apoptosis. Results: Our results establish that both cisplatin and the novel inorganic complex can inhibit the proliferation of A549, Hela, and PA 1 cells. The novel inorganic coordination complex in the study shows the IC 50 at 75 µM,150 µM, and 250 µM in Hela, A 549 and PA 1 respectively with respect to cisplatin which shows the IC 50 at 50 µM, 100 µM and 300 µM in Hela, PA 1, and A 549 respectively. After treatment with cisplatin and inorganic cooedination complex, Bax/Bcl-2 ratio was strongly up regulated in Hela cells and moderately elevated in A 549 and PA 1 cells. We demonstrate that a combination of anti proliferative measures such as delay in cell cycle progression, induction of apoptosis and generation of ROS act together to mediate the effects of cisplatin and the novel inorganic complex on cancer cells. Conclusion: The present study showed that Hela is more sensitive than A 549 and PA1 to cisplatin and the novel inorganic complex. Although the novel inorganic complex is found to be more effective anticancer agent than cisplatin in case of A 549 when compared with the other two cell lines, Hela and PA1. These results have pointed out that cisplatin and the novel inorganic complex might exert chemopreventive effect through ROS generation and induction of apoptogenic signals via mitochondrial death cascade in human lung, cervical and ovarian carcinoma cells. The novel inorganic coordination complex is more effective anticancer agent in lung carcinoma cells when compared to cervical and ovarian cancer cells. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B16.